JBC INTERFERin siRNA transfection reagent

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Volume 270, Number 22, Issue of June 2, pp. 12953-12956, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor (PPAR)

Jürgen M. Lehmann , Linda B. Moore , Tracey A. Smith-Oliver , William O. Wilkison , Timothy M. Willson , Steven A. Kliewer

Thiazolidinedione derivatives are antidiabetic agents that increase the insulin sensitivity of target tissues in animal models of non-insulin-dependent diabetes mellitus. In vitro, thiazolidinediones promote adipocyte differentiation of preadipocyte and mesenchymal stem cell lines; however, the molecular basis for this adipogenic effect has remained unclear. Here, we report that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor (PPAR), a member of the nuclear receptor superfamily recently shown to function in adipogenesis. The most potent of these agents, BRL49653, binds to PPAR with a K of approximately 40 nM. Treatment of pluripotent C3H10T1/2 stem cells with BRL49653 results in efficient differentiation to adipocytes. These data are the first demonstration of a high affinity PPAR ligand and provide strong evidence that PPAR is a molecular target for the adipogenic effects of thiazolidinediones. Furthermore, these data raise the intriguing possibility that PPAR is a target for the therapeutic actions of this class of compounds.



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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.